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1.
BMC Dermatol ; 20(1): 6, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867747

RESUMO

BACKGROUND: Specific species of ceramides (Cer), major constituents of lipids in the stratum corneum (SC), are decreased and are correlated with SC barrier and water-holding functions in the skin of patients with atopic dermatitis (AD) or psoriasis (Pso). However, possible correlations between Cer subclass ratios and skin properties in barrier-disrupted skin and in healthy skin remain unclear. The objective of this study was to identify a new marker to evaluate skin properties and epidermal differentiation in SC not only in barrier-disrupted skin but also in healthy skin. METHODS: The Cer subclass ratios in the SC of healthy control subjects and in patients with AD or Pso were evaluated. Correlations with candidate markers and facial skin features of healthy Japanese females (20-74 years old, n = 210) were investigated. Variations of markers during epidermal differentiation were studied in human epidermis and in cultured keratinocytes. RESULTS: The ratios of Cer [NP]/[NS], Cer [NH]/[NS], Cer [NP]/[AS], Cer [NH]/[NS], Cer [NDS]/[AS], Cer [AH]/[AS] and Cer [EOP]/[AS] showed significant differences between non-lesional skin of AD patients and normal skin of healthy control subjects, as well as Pso patients and their healthy control subjects. The Cer [NP]/[NS] ratio was correlated with SC functional parameters (transepidermal water loss and capacitance) and with skin appearance (texture, scaling and color) even in the cheek skin of healthy female subjects. The Cer [NP]/[NS] ratio in the SC was approximately 18-times higher than in living keratinocytes, and it increased as they differentiated. CONCLUSIONS: The Cer [NP]/[NS] ratio in the SC is a potential marker for skin properties and epidermal differentiation in barrier-disrupted skin as well as in healthy skin.


Assuntos
Ceramidas/análise , Dermatite Atópica/patologia , Epiderme/química , Psoríase/patologia , Adulto , Idoso , Biomarcadores/análise , Estudos de Casos e Controles , Diferenciação Celular , Células Cultivadas , Dermatite Atópica/diagnóstico , Epiderme/patologia , Feminino , Humanos , Queratinócitos/química , Queratinócitos/citologia , Lipídeos/análise , Pessoa de Meia-Idade , Psoríase/diagnóstico , Adulto Jovem
2.
Sci Rep ; 10(1): 14930, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913196

RESUMO

Mast cells (MCs) are multifunctional cells of the immune system and are found in skin and all major tissues of the body. They contribute to the pathology of several diseases including urticaria, psoriasis, atopic dermatitis and mastocytosis where they are increased at lesional sites. Histomorphometric analysis of skin biopsies serves as a routine method for the assessment of MC numbers and their activation status, which comes with major limitations. As of now, non-invasive techniques to study MCs in vivo are not available. Here, we describe a label-free imaging technique to visualize MCs and their activation status in the human papillary dermis in vivo. This technique uses two-photon excited fluorescence lifetime imaging (TPE-FLIM) signatures, which are different for MCs and other dermal components. TPE-FLIM allows for the visualization and quantification of dermal MCs in healthy subjects and patients with skin diseases. Moreover, TPE-FLIM can differentiate between two MC populations in the papillary dermis in vivo-resting and activated MCs with a sensitivity of 0.81 and 0.87 and a specificity of 0.85 and 0.84, respectively. Results obtained on healthy volunteers and allergy and mastocytosis patients indicate the existence of other MC subpopulations within known resting and activated MC populations. The developed method may become an important tool for non-invasive in vivo diagnostics and therapy control in dermatology and immunology, which will help to better understand pathomechanisms involving MC accumulation, activation and degranulation and to characterize the effects of therapies that target MCs.


Assuntos
Dermatite Atópica/patologia , Hipersensibilidade/patologia , Mastócitos/citologia , Mastocitose/patologia , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Imagem Óptica/métodos , Pele/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Pré-Escolar , Dermatite Atópica/diagnóstico por imagem , Feminino , Fluorescência , Humanos , Hipersensibilidade/diagnóstico por imagem , Masculino , Mastocitose/diagnóstico por imagem , Pessoa de Meia-Idade
3.
Mol Immunol ; 126: 95-100, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32795664

RESUMO

Although T cells are considered as the central component in immune-mediated diseases, supportive evidence has demonstrated that B cells also contribute to the progression of these diseases. B cells are divided into various subsets according to their secreted cytokines. Different B cell subsets play diverse roles in immune-mediated dermatoses. Regulatory B cells (Bregs) are defined functionally by their ability to secrete IL-10, which has been revealed to contribute to immunological tolerance. Drugs that deplete B cells, such as rituximab, are now used for the treatment of several immune-mediated dermatoses. In this review, we present and discuss the current knowledge on the roles of B cells in several immune-mediate dermatoses including psoriasis, pemphigus, bullous pemphigoid, and dermatomyositis, atopic dermatitis.


Assuntos
Linfócitos B Reguladores/imunologia , Dermatite Atópica/imunologia , Dermatomiosite/imunologia , Penfigoide Bolhoso/imunologia , Pênfigo/imunologia , Psoríase/imunologia , Animais , Linfócitos B Reguladores/efeitos dos fármacos , Linfócitos B Reguladores/metabolismo , Dermatite Atópica/sangue , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Dermatomiosite/sangue , Dermatomiosite/tratamento farmacológico , Dermatomiosite/patologia , Desmogleína 3/metabolismo , Modelos Animais de Doenças , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Interleucina-10/metabolismo , Depleção Linfocítica/métodos , Penfigoide Bolhoso/sangue , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/patologia , Pênfigo/sangue , Pênfigo/tratamento farmacológico , Pênfigo/patologia , Psoríase/sangue , Psoríase/tratamento farmacológico , Psoríase/patologia , Pele/imunologia , Pele/patologia
4.
Nat Commun ; 11(1): 4092, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796837

RESUMO

Single nucleotide polymorphisms (SNPs) in the gene encoding kinesin family member 3A, KIF3A, have been associated with atopic dermatitis (AD), a chronic inflammatory skin disorder. We find that KIF3A SNP rs11740584 and rs2299007 risk alleles create cytosine-phosphate-guanine sites, which are highly methylated and result in lower KIF3A expression, and this methylation is associated with increased transepidermal water loss (TEWL) in risk allele carriers. Kif3aK14∆/∆ mice have increased TEWL, disrupted junctional proteins, and increased susceptibility to develop AD. Thus, KIF3A is required for skin barrier homeostasis whereby decreased KIF3A skin expression causes disrupted skin barrier function and promotes development of AD.


Assuntos
Dermatite Atópica/metabolismo , Cinesina/metabolismo , Pele/metabolismo , Adolescente , Adulto , Alelos , Animais , Criança , Dermatite Atópica/genética , Dermatite Atópica/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cinesina/genética , Masculino , Metilação , Camundongos , Reação em Cadeia da Polimerase em Tempo Real , Pele/patologia , Adulto Jovem
5.
Ann Allergy Asthma Immunol ; 125(5): 507-516, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32702411

RESUMO

OBJECTIVE: The origins of allergic diseases have traditionally been explained by immunoglobulin E-mediated immune responses to account for asthma, atopic dermatitis, atopic rhinitis, and food allergy. Research insights into disease origins support a broader array of factors that predispose, initiate, or exacerbate altered immunity in allergic diseases, such as (1) inherent epithelial barrier dysfunction; (2) loss of immune tolerance; (3) disturbances in the gut; and (4) organ-specific microbiomes, diet, and age. Here, we discuss these influences that together form a better understanding of allergy as a systems disease. DATA SOURCES: We summarize recent advances in epithelial dysfunction, environmental influences, inflammation, infection, alterations in the specific microbiome, and inherent genetic predisposition. STUDY SELECTIONS: We performed a literature search targeting primary and review articles. RESULTS: We explored microbial-epithelial-immune interactions underlying the early-life origins of allergic disorders and evaluated immune mechanisms suggesting novel disease prevention or intervention strategies. Damage to epithelial surfaces lies at the origin of various manifestations of allergic disease. As a sensor of environmental stimuli, the epithelium of the lungs, gut, and skin is affected by an altered microbiome, air pollution, food allergens in a changed diet, and chemicals in modern detergents. This collectively leads to alterations of lung, skin, or gut epithelial surfaces, driving a type 2 immune response that underlies atopic diseases. Treatment and prevention of allergic diseases include biologics, oral desensitization, targeted gut microbiome alterations, and changes in behavior. CONCLUSION: Understanding the spectrum of allergy as a systems disease will allow us to better define the mechanisms of allergic disorders and improve their treatment.


Assuntos
Microbioma Gastrointestinal/imunologia , Hipersensibilidade/imunologia , Mucosa Intestinal/imunologia , Mucosa Respiratória/imunologia , Pele/imunologia , Asma/imunologia , Asma/patologia , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Progressão da Doença , Epitélio/imunologia , Epitélio/metabolismo , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/patologia , Humanos , Mucosa Intestinal/microbiologia , Permeabilidade , Rinite Alérgica/imunologia , Rinite Alérgica/patologia , Pele/patologia , Resultado do Tratamento
6.
Ann Allergy Asthma Immunol ; 125(6): 686-692.e3, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32682980

RESUMO

BACKGROUND: Little is known about the longitudinal course of adult atopic dermatitis (AD) lesional severity and extent in clinical practice. OBJECTIVE: To determine the longitudinal course of AD in clinical practice. METHODS: A prospective, dermatology practice-based study was performed (n = 400). Patients were assessed at baseline and approximately 6, 12, 18, and 24 months by eczema area and severity index (EASI) and objective-scoring atopic dermatitis (objective-SCORAD). Multivariable repeated measures linear regression models were constructed to evaluate AD severity over time. RESULTS: Overall, 36.2% and 18.2% of patients had moderate (6.0-22.9) or severe (23.0-72.0) EASI scores at any visit, respectively. Similarly, 29.0% and 26.4% of patients had moderate (24.0-37.9) or severe (38.0-83.0) objective-SCORAD scores at any visit, respectively. Among patients with baseline moderate (6.0-22.9) or severe (23.0-72.0) EASI scores, 25.0% and 18.6% continued to have moderate or severe scores at 1 or more follow-up visits, respectively. Similarly, among patients with baseline moderate (24.0-37.9) or severe (38.0-83.0) objective-SCORAD scores, 22.6% and 24.5% continued to have moderate or severe scores at 1 or more follow-up visits, respectively. In longitudinal regression models, EASI was significantly associated with body surface area (adjusted ß [95% confidence interval]: 0.16 [0.09-0.23]) and edema/papulation (2.31 [0.19-4.43]). In addition, objective-SCORAD was significantly associated with body surface area (0.12 [0.04-0.21]), edema/papulation (4.69 [2.05-7.32]), and scratch (3.34 [0.45-6.24]) over time. CONCLUSION: AD lesional severity has a heterogeneous longitudinal course. Many patients had fluctuating lesional severity scores over time. A minority of patients had persistently moderate or severe lesions over time. Most patients with moderate-severe disease at baseline were unable to achieve persistent lesional clearance.


Assuntos
Dermatite Atópica/patologia , Pele/patologia , Adulto , Dermatite Atópica/fisiopatologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Índice de Gravidade de Doença , Fatores de Tempo
7.
Life Sci ; 258: 118139, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32721463

RESUMO

AIMS: Atopic dermatitis is a chronic inflammatory disease characterized by eczematous lesions and has become a serious health problem worldwide. Pseudoephedrine (PSE) is a nasal decongestant to treat the common cold. PSE has been reported that is beneficial to allergic diseases. However, whether PSE has the potential in atopic dermatitis remains to be elucidated. MAIN METHODS: Male BALB/c mice were challenged with 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like lesion and orally administrated with PSE for two weeks. The skin hydration and the scratching behavior were detected. The skin lesions and histopathological changes were evaluated and inflammatory factors levels were detected. Human Keratinocytes (HaCaT cells) were stimulated by TNF-α/IFN-γ after PSE-pretreatment. The transcriptions of inflammatory factors were detected. KEY FINDINGS: PSE decreased skin lesion area and skin thickness in atopic dermatitis mice. PSE improved skin hydration and scratching. Histologically, PSE reduced mast cell and CD4+ cell infiltration. PSE suppressed serum TNF-α and IgE levels, reducing cytokines (IL-1ß, IL-4, IL-6, IL-13, IL-33, TSLP, and IL-23) and neutrophil migration factors (CCL2 and MMP-9) in skin tissues. In addition, PSE inhibited TNF-α/IFN-γ-induced release of inflammatory factors (TNF-α, IL-1ß, and IL-23) in HaCaT cells. Furthermore, PSE suppressed the activation of MAPKs and NF-κB signaling pathways in vivo and in vitro. SIGNIFICANCE: These results demonstrate that PSE could inhibit inflammatory responses in atopic dermatitis models. PSE may serve as a viable alternatives drug for the treatment of atopic dermatitis.


Assuntos
Dermatite Atópica/tratamento farmacológico , Inflamação/tratamento farmacológico , Pseudoefedrina/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Dermatite Atópica/sangue , Dermatite Atópica/enzimologia , Dermatite Atópica/patologia , Humanos , Imunoglobulina E/sangue , Inflamação/sangue , Inflamação/patologia , Interferon gama/farmacologia , Masculino , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Pseudoefedrina/química , Pseudoefedrina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/patologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/farmacologia
8.
PLoS One ; 15(7): e0235500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614886

RESUMO

INTRODUCTION: Clinical trials often suffer from significant recruitment barriers, poor adherence, and dropouts, which increase costs and negatively affect trial outcomes. The aim of this study was to examine whether making it virtual and reward-based would enable nationwide recruitment, identify patients with variable disease severity, achieve high adherence, and reduce dropouts. METHODS: In a siteless, virtual feasibility study, individuals with atopic dermatitis (AD) were recruited online. During the 8-week study, subjects used their smartphones weekly to photograph target AD lesions, and completed patient-oriented eczema measure (POEM) and treatment use questionnaires. In return, subjects were rewarded every week with personalized lifestyle reports based on their DNA. RESULTS: Over the course of the 11 day recruitment period, 164 (82% women and 18% men) filled in the form to participate, of which 65 fulfilled the inclusion criteria and signed the informed consent. Ten were excluded as they did not complete the mandatory study task of returning the DNA sample. 55 (91% women, 9% men) subjects returned the DNA sample and were enrolled throughout Denmark, the majority outside the Copenhagen capital region in rural areas with relatively low physician coverage. The mean age was 28.5 (SD ±9.5 years, range 18-52 years). The baseline POEM score was 14.5±5.6 (range 6-28). Based on the POEM, 7 individuals had mild, 28 had moderate, 17 had severe, and 3 had very severe eczema. The retention rate was 96% as 53 out of 55 enrolled completed the study. The adherence was very high, and more than 90% of all study tasks were completed. Follow up of 41 subjects showed that 90% would take part again or continue if the study had been longer. CONCLUSION: A virtual trial design enables recruitment with broad geographic reach and throughout the full spectrum of disease severity. Providing personalized genetic reports as a reward seems to contribute to high adherence and retention.


Assuntos
Dermatite Atópica/psicologia , Eczema/patologia , Recompensa , Cooperação e Adesão ao Tratamento , Adolescente , Adulto , DNA/análise , Dermatite Atópica/genética , Dermatite Atópica/patologia , Dermatite Atópica/terapia , Fármacos Dermatológicos/uso terapêutico , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fototerapia , Índice de Gravidade de Doença , Smartphone , Inquéritos e Questionários , Adulto Jovem
9.
PLoS One ; 15(7): e0235295, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687504

RESUMO

Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and lymphoid organ defects. To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice. Limiting expression to keratinocytes (using a Krt14-cre) induced a chronic eosinophilic dermatitis, but no inflammation in other organs or lymphoid organ defects. The dermatitis was associated with a markedly increased concentration of serum IgE and IL18. Crosses with S100a4-cre resulted in milder skin lesions and moderate to severe arthritis. This conditional null mutant will enable more detailed studies on the role of SHARPIN in regulating NFkB and inflammation, while the Krt14-Sharpin-/- provides a new model to study atopic dermatitis.


Assuntos
Dermatite Atópica/genética , Inflamação/genética , Queratina-14/genética , Proteínas do Tecido Nervoso/genética , Proteína A4 de Ligação a Cálcio da Família S100/genética , Animais , Apoptose/genética , Artrite/genética , Artrite/patologia , Dermatite Atópica/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Humanos , Imunoglobulina E/genética , Inflamação/patologia , Integrases/genética , Interleucina-18/genética , Queratinócitos/metabolismo , Queratinócitos/patologia , Camundongos , NF-kappa B/genética , Fenótipo , Transdução de Sinais
10.
Lancet ; 396(10246): 255-266, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711801

RESUMO

BACKGROUND: Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis. METHODS: In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index [EASI] score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060. FINDINGS: Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 [24%] of 156 patients vs six [8%] of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 [44%] of 153 patients vs six [8%] of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 [40%] of 156 patients vs nine [12%] of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 [63%] of 153 patients vs nine [12%] of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported. INTERPRETATION: Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis. FUNDING: Pfizer.


Assuntos
Dermatite Atópica/tratamento farmacológico , Eczema/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Austrália/epidemiologia , Canadá/epidemiologia , Estudos de Casos e Controles , Criança , Dermatite Atópica/patologia , Método Duplo-Cego , Eczema/patologia , Grupos Étnicos , Europa (Continente)/epidemiologia , Feminino , Humanos , Janus Quinase 1/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Segurança , Índice de Gravidade de Doença , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Estados Unidos/epidemiologia
11.
Medicine (Baltimore) ; 99(22): e20329, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481406

RESUMO

Parental knowledge regarding the role of moisturizers in restoring the skin barrier, as well as regular and long-term use of moisturizers, is critical in the treatment of infantile eczema and the prevention of relapse.The parents of children with eczema were enrolled in this study. Their knowledge of the role, use, and effect of moisturizers on their children, as well as their concerns regarding moisturizers were surveyed.A total of 350 parents were enrolled in this study. Two hundred fifty-two parents (72%) knew that eczema requires moisturizers to restore the skin barrier. Among these 252 parents, 175 parents (50.0%) knew that moisturizers can restore the skin barrier. Only 27 parents (27/175, 15.4%) of them knew that moisturizers can improve eczema. Overall, 69.4% used moisturizers; of these, 75.3% used only moisturizers on the face, 87.2% on dry areas of face and other body parts, and only 6.6% on the entire body. Furthermore, 13.2% used topical moisturizers in the long-term; 62.6% used moisturizers 1 to 2 times per day, while 5.4% used moisturizers once every few days. A total of 80.7% discontinued moisturizers immediately after improvement in dryness, and 75.3% reported skin dryness despite moisturizer usage. Among parents of children who used moisturizers, 16.5% were worried about the side effects of moisturizers.Despite a fair level of knowledge about moisturizers, parents of children with eczema are using them inadequately. Pediatrician should be more patient to educate parents the information on the importance of moisturizers for the improvement of eczema and prevention of recurrence.


Assuntos
Dermatite Atópica/terapia , Conhecimentos, Atitudes e Prática em Saúde , Creme para a Pele/uso terapêutico , Dermatite Atópica/patologia , Feminino , Humanos , Lactente , Masculino , Pais , Índice de Gravidade de Doença , Pele/patologia , Creme para a Pele/administração & dosagem
12.
PLoS One ; 15(5): e0225675, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469869

RESUMO

A cross-sectional hypothesis generating study was performed to investigate modifiable exposures such as whether feeding pattern (a non-processed meat based diet, NPMD, or an ultra-processed carbohydrate based diet, UPCD), certain environmental factors and their timing of exposure might be associated with the development of canine atopic dermatitis (CAD). Also, genetic and demographic factors were tested for associations with CAD. The data was collected from the validated internet-based DogRisk food frequency questionnaire in Finland. A total of 2236 dogs were eligible for the study (the owners reported 406 cases and 1830 controls). Our main interest was to analyze modifiable early risk factors of CAD, focusing on nutritional and environmental factors. We tested four early life periods; prenatal, neonatal, early postnatal and late postnatal periods. Twenty-two variables were tested for associations with CAD using logistic regression analysis. From the final models we identified novel dietary associations with CAD: the NPMD during the prenatal and early postnatal periods had a significant negative association with the incidence of CAD in adult dogs (age above 1 year). Oppositely, UPCD was associated with a significantly higher risk for CAD incidence. Other variables that were associated with a significantly lower risk for CAD were maternal deworming during pregnancy, sunlight exposure during early postnatal period, normal body condition score during the early postnatal period, the puppy being born within the same family that it would stay in, and spending time on a dirt or grass surface from 2 to 6 months. Also, the genetic factors regarding maternal history of CAD, allergy-prone breeds and more than 50% white-colored coat all showed a significant positive association with CAD incidence in agreement with previous findings. Although no causality can be established, feeding NPMD early in life seemed to be protective against CAD, while UPCD could be considered a risk factor. Prospective intervention studies are needed to establish the causal effects of the protective role of NPMD on prevalence of CAD during the fetal and early postnatal life.


Assuntos
Dermatite Atópica/diagnóstico , Dieta/efeitos adversos , Doenças do Cão/diagnóstico , Exposição Ambiental/efeitos adversos , Animais , Dermatite Atópica/etiologia , Dermatite Atópica/patologia , Doenças do Cão/etiologia , Doenças do Cão/patologia , Cães , Comportamento Alimentar/fisiologia , Humanos , Internet , Fatores de Risco , Inquéritos e Questionários
13.
Adv Exp Med Biol ; 1253: 107-140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32445093

RESUMO

Atopic Dermatitis (AD) is a common inflammatory disease with a genetic background. The prevalence of AD has been increasing in many countries. AD patients often have manifestations of pruritus, generalized skin dryness, and eczematous lesions. The pathogenesis of AD is complicated. The impaired skin barrier and immune imbalance play significant roles in the development of AD. Environmental factors such as allergens and pollutants are associated with the increasing prevalence. Many genetic and environmental factors induce a skin barrier deficiency, and this can lead to immune imbalance, which exacerbates the impaired skin barrier to form a vicious cycle (outside-inside-outside view). Genetic studies find many gene mutations and genetic variants, such as filaggrin mutations, which may directly induce the deficiency of the skin barrier and immune system. Epigenetic studies provide a connection between the relationship of an impaired skin barrier and immune and environmental factors, such as tobacco exposure, pollutants, microbes, and diet and nutrients. AD is a multigene disease, and thus there are many targets for regulation of expression of these genes which may contribute to the pathogenesis of AD. However, the epigenetic regulation of environmental factors in AD pathogenesis still needs to be further researched.


Assuntos
Dermatite Atópica/genética , Epigênese Genética , Interação Gene-Ambiente , Dermatite Atópica/patologia , Eczema/genética , Humanos , Sistema Imunitário , Pele/patologia
14.
Sci Rep ; 10(1): 7968, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409755

RESUMO

The diagnostic possibilities of multiphoton tomography (MPT) in dermatology have already been demonstrated. Nevertheless, the analysis of MPT data is still time-consuming and operator dependent. We propose a fully automatic approach based on convolutional neural networks (CNNs) to fully realize the potential of MPT. In total, 3,663 MPT images combining both morphological and metabolic information were acquired from atopic dermatitis (AD) patients and healthy volunteers. These were used to train and tune CNNs to detect the presence of living cells, and if so, to diagnose AD, independently of imaged layer or position. The proposed algorithm correctly diagnosed AD in 97.0 ± 0.2% of all images presenting living cells. The diagnosis was obtained with a sensitivity of 0.966 ± 0.003, specificity of 0.977 ± 0.003 and F-score of 0.964 ± 0.002. Relevance propagation by deep Taylor decomposition was used to enhance the algorithm's interpretability. Obtained heatmaps show what aspects of the images are important for a given classification. We showed that MPT imaging can be combined with artificial intelligence to successfully diagnose AD. The proposed approach serves as a framework for the automatic diagnosis of skin disorders using MPT.


Assuntos
Inteligência Artificial , Dermatite Atópica/diagnóstico por imagem , Tomografia/métodos , Dermatite Atópica/patologia , Humanos , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Imagem Óptica/métodos , Imagem Óptica/normas , Curva ROC , Tomografia/normas
15.
Artigo em Inglês | MEDLINE | ID: mdl-32397578

RESUMO

Background: The territorial expansion and increased population size of haematophagous arthropods (i.e., the castor bean tick Ixodes ricinus (Ixodida: Ixodidae) and the deer ked Lipoptena cervi (Diptera: Hippoboscidae)) has enhanced the risk of human infestations in Europe. The aim of our study was to present skin lesions induced by tick and deer ked bites in patients from recreational forest regions in southeastern Poland and pay attention to features of skin changes that may be useful in differential diagnosis. Methods: We compare the skin lesions after I. ricinus and L. cervi bite and draw attention to the biological and ecological traits of both ectoparasites, which may be diagnostically relevant for determination of the cause of skin symptoms reported by patients. Results: I. ricinus bites lead to development of erythematous-infiltrative poorly demarcated lesions with a centrally located bite mark, which usually disappears within one to several days. In turn, L. cervi bites leave irregularly shaped scattered erythematous papules. The papules may persist for up to one year and are accompanied by itching. Conclusions: Correct assessment of the clinical picture and its association with an arthropod bite (e.g., tick or deer ked) is highly important for further diagnostic procedures (i.e., differentiation of skin lesions developing in tick-borne diseases and, consequently, correct choice of pharmacological therapy). I. ricinus and L. cervi differ in their developmental cycles and rhythms of activity, which indicates that both species should be considered potential causative agents in the differential diagnosis of skin lesions when the patient has been bitten by an arthropod in autumn and winter months.


Assuntos
Cervos/parasitologia , Dermatite Atópica/etiologia , Dípteros , Mordeduras e Picadas de Insetos/patologia , Ixodes , Doenças Parasitárias em Animais/epidemiologia , Animais , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Europa (Continente)/epidemiologia , Humanos , Mordeduras e Picadas de Insetos/imunologia , Polônia/epidemiologia
16.
Sci Rep ; 10(1): 8417, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32439906

RESUMO

The main factors involved in the pathogenesis of atopic dermatitis (AD) are skin barrier abnormality, allergy/immunology, and pruritus. Considering how oxidative stress influences these factors, antioxidant agents may be effective candidates in the treatment of AD. To evaluate the effect of Caffeoyl-Pro-His amide (CA-PH), an antioxidant agent, on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like phenotypes in BALB/c mice. Topical sensitization and challenge by DNCB were performed on the dorsal skin of BALB/c mice to induce AD-like cutaneous lesions, phenotypes, and immunologic response. CA-PH was applied topically for 2 weeks to assess its effects on DNCB-induced AD-like phenotypes. As a result, CA-PH relieved DNCB-induced AD-like phenotypes quantified by dermatitis severity score, scratching duration, and trans-epidermal water loss. Histopathological analysis showed that CA-PH decreased epidermal thickening, the number of mast cells, and eosinophil infiltration in dermis. Immunohistochemical staining revealed that CA-PH recovered skin barrier-related proteins: filaggrin, involucrin, and loricrin. As for the immunologic aspects, CA-PH treatment lowered mRNA or protein levels of interleukin (IL)-4, IL-6, IL-17a, IL-1b, IL-31, and IL-33 levels and thymic stromal lymphopoietin (TSLP) levels in cutaneous tissue, reducing the DNCB-induced serum IgE level elevation. In conclusion, topical CA-PH may be a therapeutic option for the treatment of AD.


Assuntos
Amidas/farmacologia , Antioxidantes/farmacologia , Ácidos Cafeicos/farmacologia , Dermatite Atópica/tratamento farmacológico , Prurido/tratamento farmacológico , Amidas/química , Animais , Ácidos Cafeicos/química , Citocinas/metabolismo , Dermatite Atópica/patologia , Dinitroclorobenzeno/toxicidade , Eosinófilos/metabolismo , Feminino , Heme Oxigenase-1/metabolismo , Imunoglobulina E/sangue , Interleucinas/sangue , Proteínas de Filamentos Intermediários/metabolismo , Mastócitos/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Precursores de Proteínas/metabolismo , Prurido/patologia , Pele/patologia , Junções Íntimas/efeitos dos fármacos
17.
J Med Internet Res ; 22(4): e15599, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32329744

RESUMO

BACKGROUND: In recent years, YouTube has become a recognized source of medical information for health care consumers. Although YouTube has advantages in this context, there are potential dangers as videos may contain nonscientific, misleading, or even harmful information. OBJECTIVE: As little is known about YouTube as a source of information on atopic dermatitis (AD), we investigated the content-related quality of AD videos and their perception among YouTube users. METHODS: The quality of the 100 most viewed AD videos was assessed by using the Global Quality Scale (GQS) and the DISCERN instrument. Videos were classified as "useful," "misleading," and "potentially harmful," and the correlations of viewers' ratings (likes) with the GQS and DISCERN scores were assessed. RESULTS: Among the 100 videos, 68.0% (68/100) and 62.0% (62/100) were of poor and very poor scientific quality, respectively. Additionally, 32.0% (32/100) of the videos were classified as useful, 48.0% (48/100) were classified as misleading, and 34.0% (34/100) were classified as potentially harmful. Viewers' ratings did not correlate with the GQS and DISCERN scores. Overall, 50.0% (50/100) of the videos were posted by private individuals and promoters of complementary/alternative treatments, 42.0% (42/100) by therapeutical advertisers, and only 8.0% (8/100) by nonprofit organizations/universities. CONCLUSIONS: Our study demonstrated that two-thirds of the videos analyzed were below acceptable medical quality standards and that many videos were disseminating misleading or even dangerous content. Subjective and anecdotal content was overrepresented, and viewers did not appear to be able to distinguish between high- and low-quality videos. Health promotion strategies by professional medical organizations are needed to improve their presence and visibility on YouTube.


Assuntos
Dermatite Atópica/diagnóstico , Mídias Sociais/normas , Gravação em Vídeo/métodos , Gravação de Videoteipe/métodos , Estudos Transversais , Dermatite Atópica/patologia , Humanos
18.
Actas dermo-sifiliogr. (Ed. impr.) ; 111(3): 205-221, abr. 2020. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-191523

RESUMO

La dermatitis atópica es la dermatosis inflamatoria más frecuente y hasta un 20% de los casos pueden clasificarse como moderados a graves. En los últimos años se ha producido un avance en el conocimiento de la patogenia, centrada en la vía Th2, pero con una participación marcada de la vía Th22 y de los ejes Th1 y Th17, de la disfunción de la barrera epidérmica, el prurito y la señalización JAK/STAT. Este progreso ha condicionado el desarrollo de nuevas terapias sistémicas, entre las que destacan fármacos biológicos dirigidos frente a la IL-4/13, como dupilumab, tralokinumab y lebrikizumab, pero también moléculas pequeñas, como los inhibidores de JAK, entre los que se incluyen baricitinib, upadicitinib y abrocitinib. Entre las innovaciones en los tratamientos tópicos se incluyen los inhibidores de la PDE4 y de JAK/STAT. Este artículo repasa los principales avances terapéuticos en dermatitis atópica, para los que son esenciales la caracterización de los subtipos clínicos y moleculares clave en su patogénesis


Atopic dermatitis is the most common inflammatory skin disease and up to 20% of cases can be classified as moderate to severe. Our understanding of the pathogenesis of this disease has improved in recent years. The process is primarily driven by the Th2 pathway, but with significant contributions from the Th22 pathway, the Th1 and Th17 axes, epidermal barrier dysfunction, pruritus, and JAK/STAT signaling. Advances in our understanding of the pathogenesis of atopic dermatitis have led to the development of new systemic treatments. Of particular note are biologic agents targeting IL-4 and IL-13 (e. g. , dupilumab, tralokinumab, and lebrikizumab) and small molecules, such as JAK inhibitors (e. g. , baricitinib, upadacitinib, and abrocitinib). Novel topical treatments include phosphodiesterase 4 and JAK/STAT inhibitors. In this article, we review the main advances in the treatment of atopic dermatitis. Characterization of clinical and molecular phenotypes with a key pathogenic role is essential for driving these advances


Assuntos
Humanos , Dermatite Atópica/patologia , Dermatite Atópica/terapia , Administração Tópica , Produtos Biológicos , Anticorpos Monoclonais/uso terapêutico
19.
Sci Rep ; 10(1): 6451, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32296080

RESUMO

Current studies addressing the influence of interleukin-33 or its receptor (IL-33R/ST2) on development of atopic dermatitis-like inflammation in mice have reported conflicting results. We compared the response in single- and double-deficient IL-33-/-/ST2-/- C57BL/6J BomTac mice in the well-established calcipotriol-induced model of atopic dermatitis. All genotypes (groups of up to 14 mice) developed atopic dermatitis-like inflammation yet we observed no biologically relevant difference between groups in gross anatomy or ear thickness. Moreover, histological examination of skin revealed no differences in mononuclear leukocyte and granulocyte infiltration nor Th2 cytokine levels (IL-4 and IL-13). Finally, skin CD45+ cells and CD3+ cells were found at similar densities across all groups. Our findings indicate that lack of interleukin-33 and its receptor ST2 does not prevent the development of AD-like skin inflammation.


Assuntos
Dermatite Atópica/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1/deficiência , Interleucina-33/deficiência , Transdução de Sinais/imunologia , Animais , Calcitriol/análogos & derivados , Calcitriol/imunologia , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/patologia , Modelos Animais de Doenças , Feminino , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/imunologia , Interleucina-33/genética , Interleucina-33/imunologia , Masculino , Camundongos , Camundongos Knockout , Transdução de Sinais/genética , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia
20.
Int J Mol Sci ; 21(6)2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32183011

RESUMO

Dysfunctional skin barrier plays a key role in the pathophysiology of atopic dermatitis (AD), a common inflammatory skin disease. Altered composition of ceramides is regarded as a major cause of skin barrier dysfunction, however it is not clear whether these changes are intrinsic or initiated by inflammation and aberrant immune response in AD. This study investigated the levels of free sphingoid bases (SBs) sphingosine and sphinganine and their ceramides and glucosylceramide in the stratum corneum (SC) and related them to skin barrier function, disease severity and local cytokine milieu. Ceramides were measured in healthy skin, and lesional and non-lesional skin of AD patients by a novel method based on deacylation of ceramides which were subsequently determined as corresponding sphingoid bases by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The cytokine levels were determined by multiplex immunoassay. Atopic skin showed increased levels of most investigated markers, predominantly in lesional skin. The largest difference in respect to healthy skin was found for glucosylceramide with respective median values of 0.23 (IQR 0.18-0.61), 0.56 (IQR 0.32-0.76) and 19.32 (IQR 7.86-27.62) pmol/g protein for healthy, non-lesional and lesional skin. The levels of investigated ceramide markers were correlated with disease severity (scoring atopic dermatitis, SCORAD) and skin barrier function (trans-epidermal water loss, TEWL) and furthermore with cytokines involved in innate, Th-1, and Th-2 immune response. Interestingly, the strongest association with SCORAD was found for sphinganine/sphingosine ratio (r = -0.69, p < 0.001; non-lesional skin), emphasizing the importance of SBs in AD. The highest correlation with TEWL was found for glucosylceramide (r2 = 0.60, p < 0.001), which was investigated for the first time in AD. Findings that the changes in SBs and ceramide levels were predominant in lesional skin and their association with disease severity and cytokine levels suggest an immune-system driven effect. a novel analysis method demonstrates a robust and simple approach that might facilitate wider use of lipid biomarkers in the clinics e.g., to monitor (immune) therapy or dissect disease endotypes.


Assuntos
Ceramidas/metabolismo , Citocinas/metabolismo , Dermatite Atópica/metabolismo , Esfingosina/análogos & derivados , Adulto , Biomarcadores/metabolismo , Dermatite Atópica/patologia , Feminino , Humanos , Masculino , Esfingosina/metabolismo
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